This new Program Project will unite four established investigators in studies of the development and senescence of the human immune system. The Program Project evolved from the realization by Drs. Kincade, Thompson, and Webb that much very basic information available for the murine immune system is lacking for humans, making it difficult for them to extend their recent exciting findings made with mice to humans. However, new technologies make it difficult for them to extend their recent exciting findings made with mice to humans. However, new technologies and model systems now make it feasible to undertake molecular studies with human lymphocyte precursors and minor subsets of mature cells. Dr. Capra , the fourth investigator, was already, and will continue to be, focused on the human humoral immune response. The four projects are highly integrated and cover many aspects of lymphocyte development. Drs. Thompson and Kincade will study early events in the differentiation of T and B lymphocytes, respectively. Drs. Kincade and Capra will examine the effects of aging on B cell development with Dr. Kincade's efforts focused on early stages and Dr. Capra's on the alter antibody-forming phases. Dr. Webb will study the expression and function of a B cell transcription factor at all stages of forming phases. Dr. Webb will study the expression and function of a B cell transcription factor at all stages of forming phases. Dr. Webb will study the expression and function of a B cell transcription factor at all stages of B cell differentiation with a goal of understanding its role in X-linked a gamma globulinemia.. All four projects involve characterization and/or use of discrete populations of human lymphocytes, making the Flow Cytometry Core with a new MoFlo flow cytometer an integral part of the Program Project. The four investigators will share rare populations of cells as well as molecular techniques for their characterization. The smooth functioning of the Program Project is also assured through an Administrative Core. The combined efforts of the four Project Leaders will yield new insights into the molecular events in human lymphocyte development and abnormalities which occur in immunodeficiencies, autoimmunity, malignancies, and aging.